Environmental perturbations lift the degeneracy of the genetic code to regulate protein levels in bacteria
Environmental perturbations lift the degeneracy of the genetic code to regulate protein levels in bacteria
复制标题
DOI：
10.1073/pnas.1211077110
复制
发表时间：
2013-02-05
影响因子：
11.1
通讯作者：
Cluzel, Philippe
中科院分区：
文献类型：
--
作者：
Subramaniam, Arvind R.;Pan, Tao;Cluzel, Philippe
作为蛋白质合成基础的遗传密码是退化生物系统的典型例子。物理和生物系统中的简并可以通过外部扰动来解除，从而允许简并系统表现出广泛的行为。在这里，我们表明，遗传密码的简并性被环境扰动解除，以调节活细胞中的蛋白质水平。通过测量蛋白质合成率从大肠杆菌中的合成报告库，我们发现，环境扰动，如同源氨基酸供应的减少，解除遗传密码的简并性分裂密码子家族到一个层次的强大和敏感的同义密码子。在这些条件下，与稳健密码子相关的蛋白质合成速率比与敏感密码子相关的蛋白质合成速率高100倍。我们发现，观察到的同义密码子之间的层次结构是不确定的通常规则与tRNA丰度和密码子的使用。相反，氨酰化的tRNA异受体之间的竞争是蛋白质合成稳健性的基础。值得注意的是，使用合成文库建立的层次结构也解释了E.杆菌我们进一步发现，相同的层次结构反映在氨基酸生物合成基因的同义突变的健身成本和σ因子基因的转录控制。我们的研究表明，生物体可以利用简并提升作为一种通用策略，以适应其环境的蛋白质合成。
The genetic code underlying protein synthesis is a canonical example of a degenerate biological system. Degeneracies in physical and biological systems can be lifted by external perturbations, thus allowing degenerate systems to exhibit a wide range of behaviors. Here we show that the degeneracy of the genetic code is lifted by environmental perturbations to regulate protein levels in living cells. By measuring protein synthesis rates from a synthetic reporter library in Escherichia coli, we find that environmental perturbations, such as reduction of cognate amino acid supply, lift the degeneracy of the genetic code by splitting codon families into a hierarchy of robust and sensitive synonymous codons. Rates of protein synthesis associated with robust codons are up to 100-fold higher than those associated with sensitive codons under these conditions. We find that the observed hierarchy between synonymous codons is not determined by usual rules associated with tRNA abundance and codon usage. Rather, competition among tRNA isoacceptors for aminoacylation underlies the robustness of protein synthesis. Remarkably, the hierarchy established using the synthetic library also explains the measured robustness of synthesis for endogenous proteins in E. coli. We further found that the same hierarchy is reflected in the fitness cost of synonymous mutations in amino acid biosynthesis genes and in the transcriptional control of sigma-factor genes. Our study suggests that organisms can exploit degeneracy lifting as a general strategy to adapt protein synthesis to their environment.